This invention relates to a dry analytical film chip which is a small piece of dry analytical film cut into a specific form, such as square, rectangle, circle or ellipsoid. The dry analytical film has a reagent layer wherein chemical reaction, biochemical reaction or immunological reaction occurs with a predetermined biochemical substance (hereinafter referred to as analyte) contained in a sample solution, such as blood or urine to produce an optical density change.
In general, to analyze qualitatively or quantitatively a specific component or an activity of a specific component in a sample solution is conducted in various industrial fields. Particularly, it is very important to analyze quantitatively the content or activity of a biochimical component or the content of a solid component of a body fluid, such as blood or urine, of an organism in the field of linical biochemical analysis.
Recently, various dry integral multilayer analytical films (also called multilayer analytical element) have been developed which can determine the content or activity of a specific analyte or the content of a specific solid component by merely spotting a small droplet of a sample solution (JSP 3,992,158, U.S. Pat. No. 4,292,272, Japanese Patent KOKAI No. 57-42951, etc.), and put to practical use. Filter paper-type test pieces and modifications thereof composed of single layer or multilayers were also proposed (U.S. Pat. No. 4,477,575), and are, in part, put to practical use. Since a sample solution can be analyzed simply and rapidly by using the dry analytical films compared with conventional wet analysis to use the dry analytical films is particularly useful for a medical organization or laboratory where a great number of sample solutions are analyzed.
As a method of analyzing an analyte of a sample solution quantitatively by using the dry analytical film, the sample solution was spotted onto the dry analytical film (when there is a spreading layer, onto the spreading layer, on the other hand, when there is no spreading layer, onto the reagent layer directly), and is kept at a definite temperature (incubated) for a predetermined period in an incubator (oven) to induce a coloring reaction (dye-forming reaction). Subsequently, light for measurement containing a wavelength, which has been previously selected by the combination of a specific analyte in a sample solution and a reagent contained in a dry analytical film, is irradiated to the dry analytical film, and the optical density is measured. The concentration or activity of the analyte in the sample solution is determined by applying the optical density to a calibration curve indicating the correlation between the optical density and the concentration or activity of the analyte which has been previously determined.
The above dry analytical film is composed of at least one layer of a reagent layer provided on a support formed of an organic polymer, preferably further a spreading layer provided on the upper side of the reagent layer. The dry analytical film is formed into a chip, and put in a slide frame made of organic polymer (called analytical slide) in order to treat by automatic operation. The slide frame also functions to keep the dry analytical film flat which tends to deform in dry conditions.
However, analyzers using the above analytical slides tend to be a big apparatus. That is, in a big medical organization, since a great quantity of analytical slides is expended in a short period, a big size cartridge is used. Moreover, it is necessary to provide the number of cartridges corresponding to the number of the analytes, and thereby, the space for setting cartridge becomes large.
Besides, the cost of the slide frame is great, and elevates the cost of the analytical slide, and the presence of the slide frame itself makes the size of cartridges and incubator greater.
Thereupon, the inventors developed an analyzer for dry analysis which can use dry analytical film chips as it is (without mounted in a slide frame) (EP 0 567 057 A).
A representative embodiment of the analyzer for dry analysis is, as shown in FIG. 13, provided with a dry analytical film chip storing portion 20 for storing virgin dry analytical film chips 10, a dry analytical film chip conveying portion 30 for taking out the dry analytical film chips 10 from the storing portion 20 and delivering to the incubator described below, a spotting portion 40 for spotting a liquid sample onto the dry analytical film chip 10 during conveying in the conveying portion 30, an incubator 50 for keeping the dry analytical film chip 10 onto which the sample liquid has been spotted at a constant temperature for a predetermined time, a photometric portion 60 for measuring the reflection optical density of the dry analytical film chip 10 wherein a coloring reaction has occured in the incubator 50, and a discharge portion 70 of the dry analytical film chip for discharging the dry analytical film chip 10 which has been measured at the photometric portion 60 from the incubator 50.
In the incubator 50, an incubator body 51 in a disc form is rotatably supported. The incubator body 51 contains a heating means (not illustrated) which keep the inside at a constant temperature around 37.degree. C . Many insertion holes 52 are formed on the circumferential side end of the body 51 at regular intervals for inserting the dry analytical film chip 10, and followed by placing parts 53 for placing the dry analytical film chip 10.
As shown in FIGS. 14 and 15, the placing part 53 has a rectangular planar form greater than the dry analytical film chip 10, and each corner 54 is projected toward the inside by rounding. Each corner of the dry analytical film chip 10 is caught by the rounded corner 54, and thereby, the sides edges of the dry analytical film chip 10 do not contact the side walls of the placing part 53. A photometric window 55 is formed at the center of the placing part 53, and a ring groove 56 into which a photometric head described later enters is formed at the underside of the photometric window 55. A taper 57 is formed above the periphery of the placing part 53 in order to guide the dry analytical film chip 10, and a cover 58 is provided movable in the vertical direction above the placing part 55 so as to prevent the evaporation of the liquid sample. Moreover, presser zigs 59 are formed at four corner portions on the underside of the cover 58 in order to rectify the deformation of the dry analytical film chip 10 by pressing.
However, it was found that, in the above analyzer using the conventional dry analytical film chips, when the dry analytical film chip has a spreading layer composed of a microporous material, liquid sample spreads to reach ends of the spreading layer and effuses from the edges. In the case of a liquid sample having a low viscosity, the liquid sample diffuses on the surface of a spreading layer or a reagent layer (particularly, in the case of a dry analytical film chip not having a spreading layer) a reagent layer to reach edges of the reagent layer, and effuses from the edges. As a result, there is a possibility that the analyzer is stained at the incubator, the photometric portion, the discharging portion, or the like, or another dry analytical film chip which has been spotted with a liquid sample but not measured photometrically yet is stained (or contaminated).
That is, since the dry analytical film chip is deformed by drying, it is pressed by the cover having the presser zigs at the placing part of the dry analytical film chip in the incubator. Accordingly, if the liquid sample spotted onto the dry analytical film chip spreads to reach the vicinity of four (4) corners, when the presser zigs press the dry anaytical film chip, the presser zigs are stained by adhering the liquid sample. The subsequent dry analytical film chip is pressed by the stained presser zigs, and results in stained by the previous liquid sample.
Moreover, if the liquid sample which has reached edges of the dry analytical film chip by spreading effuses from the edges, the edges are wet by the liquid sample. Since the placing part for the dry analytical film chip in the incubator is arranged so that the inner wall of the placing part contact edge of four corners of the dry analytical film chip in order to position the dry analytical film chip, the liquid sample spotted onto the dry analytical film chip adheres onto the wall of the placing part at the contact position, and occasionally stains the bottom of the placing part as well as the wall portion. The adhered liquid sample stains the next dry analytical film chip.
Since the dry analytical film chips are transferred to the photometric portion, the discharging portion and the like successively, the liquid sample effused from edges adheres to stain the photometric portion, the discharging portion and the like. Particularly, when the liquid sample is a biological body fluid represented by blood, the incubator is stained by the biological body fluid at the incubator, the presser zigs, the photometric portion, the discharging portion or the like. Since the body fluid has a possibility to contain pathogenic bacteria, fungi or viruses, the analyzing operator is in danger of falling into the infection with them. Accordingly, it is very undesirable is sanitary viewpoint.
The above staining troubles can be aboided by reducing the spotting amount of liquid samples, but measuring accuracy is degraded thereby.
Furthermore, the aforementioned dry analytical film chip has a difficulty in a photometry with a high accuracy. That is, the dry analytical film chip having a spreading layer composed of a porous material, such as fabric, nonwoven fabric and filter paper, hereinafter "fabric" is occasionally used as a representative of the above fibrous porous materials forms frays at edges of the spreading layer. Fiber dust generates from the frays, and adversely affects photometric results.